Does CBD prevent psychosis-like behavior in mice through epigenetic changes?

A mouse study found that CBD prevented disruptions in sensorimotor gating caused by psychosis-mimicking drugs, with effects lasting 24 hours and involving DNA methylation changes in the ventral striatum.

Pedrazzi, João F C et al.·Progress in neuro-psychopharmacology & biological psychiatry·2021·Preliminary EvidenceAnimal StudyAnimal Study
RTHC-03422Animal StudyPreliminary Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Animal Study
Evidence
Preliminary Evidence
Sample
Not reported

What This Study Found

CBD (30 and 60 mg/kg) attenuated amphetamine- and MK-801-induced disruption of prepulse inhibition, similar to clozapine. Amphetamine increased global DNA methylation in the ventral striatum, an effect prevented by CBD. CBD and clozapine both independently increased DNA methylation in the prefrontal cortex. CBD's antipsychotic-like effects persisted for 24 hours after a single dose.

Key Numbers

CBD 30 and 60 mg/kg both effective; clozapine 5 mg/kg as comparator; amphetamine 5 mg/kg and MK-801 0.5 mg/kg as psychosis models; effects detectable 24 hours after single dose; DNA methylation changes in ventral striatum and prefrontal cortex

How They Did This

Controlled animal study in mice using the prepulse inhibition (PPI) model. Tested single injections of CBD (30 or 60 mg/kg) or clozapine (5 mg/kg) followed by amphetamine (5 mg/kg) or MK-801 (0.5 mg/kg). Assessed PPI disruption and global DNA methylation in ventral striatum and prefrontal cortex via Western blot.

Why This Research Matters

This study suggests a novel mechanism for CBD's antipsychotic-like effects: modifying DNA methylation patterns. Epigenetic changes could explain why CBD effects outlast the drug's presence in the body and point toward longer-lasting therapeutic potential.

The Bigger Picture

Epigenetic mechanisms like DNA methylation can produce lasting changes in gene expression without altering DNA sequence. If CBD works partly through epigenetic modification, it could explain sustained benefits and distinguish it from conventional antipsychotics that primarily work through receptor blockade.

What This Study Doesn't Tell Us

Animal study with limited translatability. Global DNA methylation is a blunt measure that does not identify which specific genes are affected. PPI disruption is a proxy for sensorimotor gating deficits in schizophrenia but does not model the full disorder.

Questions This Raises

  • ?Which specific genes are affected by CBD-induced DNA methylation changes?
  • ?Does repeated CBD dosing produce cumulative epigenetic effects?
  • ?Could epigenetic markers serve as biomarkers for CBD response in psychosis patients?

Trust & Context

Key Stat:
Effects lasted 24 hours; epigenetic changes detected
Evidence Grade:
Well-controlled animal study with appropriate pharmacological comparators, but preclinical only with a blunt epigenetic measure.
Study Age:
Published in 2021; epigenetic mechanisms of cannabinoids remain a relatively new research area.
Original Title:
Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum.
Published In:
Progress in neuro-psychopharmacology & biological psychiatry, 111, 110352 (2021)
Database ID:
RTHC-03422

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / Observational
Case Report / Animal StudyOne case or non-human subjects
This study

Tests effects in animals (usually mice or rats), not humans.

What do these levels mean? →

Frequently Asked Questions

What are epigenetic changes?

Epigenetic changes modify how genes are expressed without changing the DNA sequence itself. DNA methylation, which this study measured, can turn genes on or off. These changes can be longer-lasting than typical drug effects.

How does this relate to treating schizophrenia?

The study used established animal models of psychosis and found CBD worked as well as the antipsychotic clozapine at preventing symptoms, while also modifying DNA methylation in brain regions involved in schizophrenia. This suggests a potential new mechanism for antipsychotic effects.

Read More on RethinkTHC

Cite This Study

RTHC-03422·https://rethinkthc.com/research/RTHC-03422

APA

Pedrazzi, João F C; Sales, Amanda J; Guimarães, Francisco S; Joca, Sâmia R L; Crippa, José A S; Del Bel, Elaine. (2021). Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum.. Progress in neuro-psychopharmacology & biological psychiatry, 111, 110352. https://doi.org/10.1016/j.pnpbp.2021.110352

MLA

Pedrazzi, João F C, et al. "Cannabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatum.." Progress in neuro-psychopharmacology & biological psychiatry, 2021. https://doi.org/10.1016/j.pnpbp.2021.110352

RethinkTHC

RethinkTHC Research Database. "Cannabidiol prevents disruptions in sensorimotor gating indu..." RTHC-03422. Retrieved from https://rethinkthc.com/research/pedrazzi-2021-cannabidiol-prevents-disruptions-in

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.